Methods of making silver nanoparticles and their applications

ABSTRACT

Disclosed herein is a method of making silver nanoparticles using an ascorbic acid derivative or an alpha-hydroxyl carboxylic acid derivative as a reducing agent. The silver nanoparticles may be coated onto micro particles, embedded in hydrogel particles or coated with polysaccharide. The silver nanoparticles may be used in a wound dressing, a bandage, a fungal treatment product, a deodorant, a floss product, a toothpick, a dietary supplement, dental X-ray, a mouthwash, a toothpaste, acne or wound treatment product, skin scrub, and skin defoliate agent.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is the U.S. National Stage of PCT/US2013/062719, filedon Sep. 30, 2013, which in turn claims the benefit of priority from U.S.provisional application No. 61/744,542, filed on Sep. 28, 2012, which isincorporated herein by reference in its entirety.

BACKGROUND

Silver can be a potential antimicrobial agent. Silver has been known topossess strong antimicrobial properties. Silver ions such as silvernitrate and sulfadiazine had been used for the treatment of burns,wounds and several bacterial infections. Their use was largelydiscontinued in the 1940s, due to the development of modern antibioticsand side effects due to the presence of ionic silver.

Silver nanoparticles have unique optical and electrical properties.Colloidal silver is one of the mostly used substrates for SurfaceEnhanced Raman Spectroscopy (SERS) for single molecule detection. Thehighly reflective silver nanoparticles have also been used in metal filmplasmonic solar cells to improve the conversion efficiency from photosto electrons. The capability of making highly conductive traces andfilms at low temperatures is of enormous commercial interest to theelectronics industry.

Silver nanoparticles can be produced by various processes such aschemical reduction of silver salts in an aqueous and organic solution,radiation assisted—chemical and photoreduction in reverse micelles,thermal decomposition of silver compounds, evaporation and condensationof silver metal, etc.

The chemical reduction methods are based on reduction of silver saltwith a number of reducing agents including sodium citrate, sodiumborohydride, hydroxylamine hydrochloride, hydrazine, andethylenediaminetetraacetic acid (EDTA), ascorbic acid, polyol, etc. Astabilizing agent needs to be added to the reaction mixture to preventthe aggregation of the silver nanoparticles formed unless the reducingagent itself is a stabilizing agent (such as citrate).

SUMMARY

Disclosed herein is a method of making silver nanoparticles, comprising:mixing a silver salt and a reducing agent with Formula I; wherein thereducing agent reduces the silver salt.

According to an embodiment, R is selected from a group consisting of H,OH, CH₃, COOH, CONH₂, a chemical species of Formula II, Formula III, orFormula IV, where n is a positive integer.

According to an embodiment, the silver salt is AgNO₃.

According to an embodiment, a molar ration of the reducing agent tosilver ion is above 0.5.

According to an embodiment, the method further comprises mixing astabilizing agent, wherein the stabilizing agent stabilizes the silvernanoparticles against aggregation.

According to an embodiment, maintaining the silver salt and the reducingagent at a temperature below 50° C.

Discloses herein is a method of making silver nanoparticles, comprising:mixing a silver salt and a reducing agent with Formula V, Formula VI, orFormula VII; wherein the reducing agent reduces the silver salt.

According to an embodiment, maintaining the silver salt and the reducingagent at a temperature above 90° C.

Disclosed herein is a method of making hydrogel particles containingsilver nanoparticles, the method comprising: preparing an emulsion witha water phase and an oil phase, the water phase comprising silvernanoparticles and polysaccharide; forming hydrogel particles from thewater phase by lowering a temperature of the emulsion while stirring.

According to an embodiment, the method further comprises dehydrating thehydrogel particles.

Disclosed herein is a micro particle with a diameter of 10-100 microns,wherein the micro particle is coated with silver nanoparticles.

According to an embodiment, the micro particle comprises calciumcarbonate or dicalcium phosphate dihydrate.

Disclosed herein is a silver nanoparticle, wherein the silvernanoparticle is coated by polysaccharide.

Disclosed herein is a method of making polysaccharide coated silvernanoparticles, the method comprising: obtaining a solution containingthe silver nanoparticles suspended therein and a stabilizing agent;replacing the stabilizing agent with polysaccharide.

Disclosed herein is a treatment product for acne or wound, comprisingthe silver nanoparticles coated by polysaccharide.

Disclosed herein is a method of treating acnes, comprising applying thesilver nanoparticles coated by polysaccharide to the acnes.

Disclosed herein is a treatment product for acne, comprising the microparticles coated with silver nanoparticles.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exemplary synthesis route of the reducing agents ofFormula I.

FIG. 2 shows an exemplary synthesis route of the reducing agents ofFormula V.

FIG. 3 shows a silver nanoparticle with polysaccharide coating andsilver nanoparticles embedded in polysaccharide micro-hydrogel.

DETAILED DESCRIPTION

Various reducing agents may be used to make silver nanoparticles byreducing silver salt. Examples of the reducing agents include sodiumcitrate, sodium borohydride (NaBH₄), hydroxylamine (NH₂OH), ascorbicacid, hydrazine (N₂H₄), and ethylene glycol. Most of these reducingagents, with exception of sodium citrate, do not stabilize silvernanoparticles. Namely, silver nanoparticles tend to aggregate. Astabilizing agent may be used to stabilize silver nanoparticles (i.e.,reduce or prevent aggregation).

Although citrate is both a reducing agent and a stabilizing agent, ittends to yield silver nanoparticles too big in size (e.g., 40-70 nmdiameter).

Others of the reducing agents may be too reactive and cause difficultiesin controlling the reduction reaction. Some of the reducing agents yieldtoxic by-products. For example, hydroxylamine (NH₂OH) generates NO;citrate generates formaldehyde. NO and Formaldehyde are gaseous, and canbe harmful if inhaled.

Lowering the redox potential of a reducing agent for the reduction ofsilver salt tends to yield more nuclei and thus smaller particle size.According to an embodiment, controlling the redox potential of areducing agent allows control of mean size of the silver nanoparticlesunder easy-to-control reaction conditions (e.g., aqueous solution,0-100° C., one atmosphere pressure), without toxic by-product or witheasily removable by-product. The reducing agent may also have chemicalfunctions that will be attached to the silver nanoparticles and thusallow various applications such as topical use for wound healing, acnetreatment, fungal treatment, dental washing, x-ray agents, appliancesurface desanitization, etc.

According to an embodiment, a reducing agent is an ascorbic acidderivative of

where R═H, OH, CH₃, COOH or CONH₂.Alternatively, R may be

where n is a positive integer.

FIG. 1 shows an exemplary synthesis route of the reducing agents ofFormula I.

According to an embodiment, a method of making silver nanoparticlesusing a reducing agent of Formula I includes mixing a silver salt suchas AgNO₃ and the reducing agent.

In an embodiment, the concentration of the silver salt after mixing isfrom 1×10⁻⁴ to 1×10⁻² mol/L. A reducing agent of Formula I may undergodifferent stages of oxidation. During the first stage, one mole of thereducing agent reduces 2 moles of the silver salt. In an embodiment, themolar ratio of the reducing agent to silver ion is above 0.5, whichreduces or essentially eliminates free silver ions in the reactionproducts.

When R is a polymer (e.g., a polymer of Formulae II, III or IV), thesilver nanoparticle is stabilized against aggregation. When R is a smallfunctional group (e.g., H, OH, CH₃, COOH or CONH₂), a stabilizing agentsuch as citric acid, polyacrylic acid (PAA), polyvinylpyrrolidone (PVP),poly(galacturonic acid) (PGUA), alginic acid may be mixed with thesilver salt and the reducing agent.

Temperature of the mix may be used to control the reaction rate (highertemperature leads to higher reaction rate) and thereby to control thesize of the silver nanoparticles. Preferably, the temperature is from 0to 100° C. at 1 atm. Preferably, the temperature is below 50° C.

The reaction usually completes within several minutes to about an hour,depending on the temperature and reagent concentration.

According to an embodiment, a reducing agent is an alpha-hydroxylcarboxylic acid derivative of

where R, R₁, R₂ may be H, OH, CH₃, COOH, CONH₂, the species of FormulaeII, III, or IV.

FIG. 2 shows an exemplary synthesis route of the reducing agents ofFormula V.

According to an embodiment, a method of making silver nanoparticlesusing a reducing agent of Formula V, VI or VII includes mixing a silversalt such as AgNO₃ and the reducing agent in a solution.

The silver salt and the reducing agent may be mixed in any suitablemethods such as (1) heating a solution of one agent (either silver salt,or the reducing agent) to a given temperature, then adding the otheragent; (2) heating a solvent (e.g., water) to a given temperatures, andadding the silver salt and the reducing agent simultaneously withagitation; or (3) mixing the silver salt and the reducing agent into asolvent at room temperature, heating the solution to a given temperatureto cause nucleation.

Preferably, the solution is heated to the boiling point of water. Forsome reducing agents such as citrate, the reaction rate at roomtemperature (about 25° C.) is very slow. At room temperature, it cantake many days to observe any nanoparticles due to slow nucleation,which leads to large size and large dispersion in size of the silvernanoparticles. At higher temperature, the reaction is faster. At 100°C., nucleation occurs within about 2 minutes.

Preferably, the solution is kept at an elevated temperature for 15-60minutes to allow the reaction to complete.

Silver nanoparticles may be collected by centrifugation. Undesirableby-products may be washed away. Silver nanoparticles may be resuspendedin a suitable medium.

According to an embodiment, silver nanoparticles prepared using thereducing agent of Formula I, V, VI or VII have a relatively narrow sizedistribution (e.g., <±20%). The diameter of the silver nanoparticles maybe controlled to be less than 50 nm. The silver nanoparticle suspensionmay have less than 1% free silver ions. The silver nanoparticlesuspension may be essentially free of free silver ions. The silvernanoparticles may be suspended in an aqueous solution and have a shelflife of more than six months. Preferably, the silver nanoparticles aresuspended in a solution with a stabilizing agent (e.g., citrate).

According to an embodiment, as schematically shown in FIG. 3, silvernanoparticles may be coated with polysaccharide. Polysaccharide coatingis digestible by bacteria and exposed silver nanoparticles may kill thebacteria. Polysaccharide coated silver nanoparticles may be suitable asfood supplement.

According to an embodiment, a method of making hydrogel particlescontaining silver nanoparticles includes:

-   preparing an water-in-oil emulsion at a temperature higher than room    temperature, the water phase containing the silver nanoparticles and    polysaccharide which can form gel when the temperature is lowed    (example agar agar);-   forming hydrogel particles from the water phase by lowering the    temperature of the emulsion while stirring;-   collecting hydrogel particles;-   washing the oil phase away.

The hydrogel particles contain the silver particles. The hydrogelparticles may be collected by centrifugation. The hydrogel particles maybe dehydrated by adding ethanol. According to an embodiment, dehydratedhydrogel particles may be used in wound dressing. Dehydrated hydrogelparticles have a dual function: reducing fluid near wound and killingbacteria.

According to an embodiment, silver nanoparticles may be used in a skinscrub/defoliate agent. Silver nanoparticles may be coated (e.g., 90%area coverage) on micro particles (e.g., calcium carbonate or dicalciumphosphate dihydrate particles of 10-100 microns diameter). The microparticles may be formed using any suitable method such as precipitation.The micro particles may be coated with silver nanoparticles in an acidicsolution because the micro particles may have a positive charge and thesilver nanoparticles may have a negative charge. The skinscrub/defoliate agent may further contain soap. The skin scrub/defoliateagent may be used to treat acnes.

According to an embodiment, an acne/wound treatment product includessilver nanoparticles coated with polysaccharide (preferably short chainpolysaccharide).

According to an embodiment, silver nanoparticles coated withpolysaccharide may be prepared using a method including: obtaining asolution containing the silver nanoparticles suspended therein and astabilizing agent (such as citric acid and small molecules); replacingthe stabilizing agent with a relatively large polysaccharide chains(e.g., at a concentration from 1 to 10 ppm).

According to an embodiment, silver nanoparticles coated withpolysaccharide may be prepared using a method including: preparingsilver nanoparticles using a reducing agent with a polysaccharide chain.

According to an embodiment, the acne treatment product may be applieddirectly to acnes or other wounds.

As an example, polysaccharide may be polygalacturonic acid (PGUA).

According to an embodiment, an acne/wound treatment product includessilver nanoparticles at a concentration of at least 10⁹ particles/ml,and the acne/wound treatment product is essentially free of silver ions.

According to an embodiment, an acne/wound treatment product includes20-42% water and about 50% micro particles coated with silvernanoparticles.

The silver nanoparticles may have other applications such as tooth pasteand mouthwash solution containing 10-100 ppm silver nanoparticles asantibacterial agent and optional 0.1-0.5% sodium fluoride (NaF) asdental cavity inhibitor.

According to an embodiment, a wound dressing includes fabric with silvernanoparticles embedded therein.

According to an embodiment, a method of making a wound dressing includesobtaining a fabric with positive charge; soaking the fabric in asuspension of silver nanoparticles; washing the fabric with water(preferably deionized water); drying the fabric. The wound dressing maybe applied directly to a wound.

According to an embodiment, a bandage includes a non-adhesive absorbentpad with polysaccharide coated silver nanoparticles embedded therein.

According to an embodiment, a fungal treatment product includes:polysaccharide coated silver nanoparticles embedded in a gel; the gelalso containing pentylene glycol, glycerine, aloe vera, trethanolamine,carbomer, PPG-2 isceteth-20 acetate, EDTA, methylparaben, and DMDMhydantoin.

According to an embodiment, a fungal treatment/deodorant productincludes silver nanoparticles suspended in a citrate solution. Thefungal treatment/deodorant product may also include methanol and/orDMSO.

According to an embodiment, a toothpaste includes 10-20 ppm or 10-100ppm of silver nanoparticles. The toothpaste may also include an abrasivesuch as dicalcium phosphate dehydrate, silicon dioxide and/or calciumcarbonate. The toothpaste may also include sodium fluoride, sorbitol,Xanthan Gum, Stevia, flavour or a combination thereof.

According to an embodiment, a toothpick or a floss product may be coatedwith silver nanoparticles.

According to an embodiment, a mouthwash includes at least 10 ppm silvernanoparticles. The mouthwash may further include NaF, pyrophosphate,hydrogen peroxide, methanol, sorbitol, sucralose, sodium saccharin,xylitol, citric acid, benzoic acid, or a combination thereof.

According to an embodiment, using the mouthwash before dental X-ray mayhelp identification of dental cavities.

According to an embodiment, a dietary supplement may include silvernanoparticles.

While specific embodiments of the invention have been described above,it will be appreciated that the invention may be practiced otherwisethan as described. The descriptions above are intended to beillustrative, not limiting. Thus it will be apparent to one skilled inthe art that modifications may be made to the invention as describedwithout departing from the scope of the appended claims.

What is claimed is:
 1. A product comprising a micro particle, whereinthe micro particle is coated with silver nanoparticles and apolysaccharide-containing coating that is digestible by bacteria,wherein the silver nanoparticles are embedded in thepolysaccharide-containing coating, wherein the micro particle haspositive charge and the silver nanoparticles have negative charge,wherein the product is configured to treat burns, wounds or bacterialinfections, wherein the micro particle comprises calcium carbonate ordicalcium phosphate dihydrate.
 2. A product of claim 1, wherein theproduct is configured to treat acne.
 3. A product of claim 1, whereinthe product is configured to scrub or defoliate skin.
 4. The product ofclaim 3, further comprising soap.
 5. The product of claim 1, wherein thesilver nano particles cover at least 90% of an area of the microparticle.
 6. The product of claim 1, wherein the polysaccharide ispolygalacturonic acid (PGUA).
 7. The product of claim 2, wherein aconcentration of silver nanoparticles is at least 10⁹ particles/ml. 8.The product of claim 2, wherein the treatment product is essentiallyfree of silver ions.
 9. The product of claim 2, wherein the treatmentproduct has a water content of 20-42%.
 10. The product of claim 2,wherein the product configured to treat acne by applying the productdirectly to acne.
 11. The product of claim 1, wherein the coating isconfigured to be digested by the bacteria resulting in the silvernanoparticles being exposed to the bacteria and killing the bacteria.12. The product of claim 1, wherein the micro particle has a diameter of10-100 microns.
 13. A product comprising a micro particle, wherein themicro particle is coated with silver nanoparticles and apolysaccharide-containing coating that is digestible by bacteria,wherein the silver nanoparticles are coated with thepolysaccharide-containing coating, wherein the micro particle haspositive charge and the silver nanoparticles have negative charge,wherein the product is configured to treat burns, wounds or bacterialinfections, wherein the micro particle comprises a calcium carbonate ordicalcium phosphate dihydrate.
 14. The product of claim 1, wherein thesilver nanoparticles are made by a method comprising: mixing a silversalt and a reducing agent with a formula

wherein the reducing agent reduces the silver salt to form the silvernanoparticles, wherein R is selected from a group consisting of H, OH,CH3, COOH, CONH2, or a chemical species of

where n is a positive integer.
 15. The product of claim 13, wherein thesilver nanoparticles are made by a method comprising: mixing a silversalt and a reducing agent with a formula

wherein the reducing agent reduces the silver salt to form the silvernanoparticles, wherein R is selected from a group consisting of H, OH,CH3, COOH, CONH2, or a chemical species of

where n is a positive integer.